Cyclohexanol-2, 2, 6, 6-tetrakis (hydroxymethyl) tetranicotinate and preparation thereof



United States Patent M This invention relates tocyclohexanol-Z,2,6,6-tetrai is- (hydroxymethyl)tetranicotinate having ageneral formula as under and the preparation thereof.

A .k Qoooorn on. onfomooo- N' N The composition of matter of thisinvention is a new compound which has not heretofore been described inthe literature. The compound can be prepared, for ex ample, by thedehydrochlorination reaction in which 4 parts of nicotinyl chloride orhydrochloric acid salt or other inorganic acid salt reacts, in thepresence or absence of a solvent, with 1 part of2,2,6,6-tetramethylolcyclohexanol.

Inert or indifferent solvents such as anhydrous benzene and toluene aresuitable for the process. Suitable deacidification agents are those ofbasic character, such as pyridine, triethyl'amine and trimethy-lamine.Those agents may, according to circumstances, function both asdeacidification agent and solvent at the same time. The reaction of thisinvention can proceed without difliculty by heating the materials at7090 C. on a Water bath for 2-3 hours.

High cholesterol food and 0.1% Normal High solution of food cholesteroleyclohexanolfood 2,2,6,6-tetrakis (hydroxylmethyl) tetranicotinateWeight of Body:

Before adminintration l6. 18i2. 33 15. 25i2. 46 16. 75:1:3. 01 Afteradministration 17. 805:3. 34 18.16:1=2. 52 19. 07:1;4. 05 In BloodSerum:

Total cholesterol,

mg. percent 110. 83 298. 33 257. 5 Ester cholesterol,

mg. percent 76. 25 224. 5 203. 75 Ester/total cholesterol 0. G88 0. 7530. 791 Triglyceride, mg.

percent 86. 0 125. 0 112. 5 Phospholipid, mg.

percent 187. 7 244 225 Phospholipid/total cholesterol 1. 694 0. 818 0.874 In Liver:

Total cholesterol,

mg. g 5.00 23. 6O 17. 90 Ester cholesterol,

mg. 2. 95 18. 80 13. 32 Phospholipid, mgJg. 34. 75 33. 70 34. 50Ester/total cholesterol 0. 590 0. 796 0. 744

3,299,977 Patented Jan. 17, 1967 Since the hydroxyl group at the1-position of 2,2,6,6- tetramethylolcyclohexanol is of different naturefrom other hydroxyl groups, the former did not react with hydrochloricacid salt of nicotinic acid chloride when 5 parts of the salt wasemployed in the otherwise same condition.

The compound of this invention evidenced useful pharmacological action.For example, a group of mice were fed for 12 days with food of highcholesterol content and a 0.1% aqueous solution ofcyclohexanol-2,2,6,6-tetrakis- (hydroxymethyl)tetranicotinate. Thecholesterol content of blood serum and liver of the mice was determinedas shown in the table.

The content of cholesterol in blood serum and in liver is explicitlylower than that in the control. This implies that the compound of thisinvention acts to remedy, i.e., counteract, the abnormal metabolism forlipid, hence it is useful for the purpose of decreasing cholesterolcontent of blood serum.

Example 1 To 'a mixture of 60 cc. of benzene, 40 cc. of pyridine and 17g. of hydrochloric acid salt of nicotinic acid chloride, was added 4.5g. of 2,2,6,6-tetramethylolcyclohexa- 1101, and the whole mixture wasrefluxed at 80 C. for 2.5 hours. After the mixture was cooled water wasadded. Precipitate formed was separated by filtration, washed thoroughlywith water and dried. Recrystallization from dilute acetic acid gave 14g. of the final compound, MP. 177-180 C.

Analysis.Calculated for C H N O C, 63.74%; H, 5.04%; N, 8.74%. Found: C,63.42%; H, 5.11%; N, 8.58%.

What is claimed is:

Cyc-lohexanol 2,2,6,6 tetrakis(hydroxylmethyDtetranicotinate having theconstitutional formula,

References Cited by the Examiner FOREIGN PATENTS 9/1963 France.

OTHER REFERENCES WALTER A. MODANCE, Primary Examiner.

ALAN L. ROTMAN, Assistant Examiner.

